The goal of this program is to develop a new process for rapidly generating mixtures of derivatives (i.e., derivative libraries) of compounds with pharmaceutical activity. Such derivatives are made from compounds possessing biological activity or from close analogues of these compounds, with the goal of identifying related compounds with more attractive pharmaceutical properties, such as aqueous solubility, GI-tract permeability, or target selectivity. The proposed process should make it possible to produce structurally distinct derivatives rapidly and to produce derivatives not readily accessible from the parent compound using traditional chemical methods. The process promises to greatly accelerate the optimization and development of pharmaceutical leads. In Phase I, it is planned to demonstrate the feasibility of this process by derivatizing known agonists of three nicotinic acetylcholine receptors - compounds that exhibit interesting neuroprotective activities but have not yet been developed into commercial pharmaceuticals. In Phase II, the process and reactor design would be optimized for rapidly generating derivative libraries from a range of starting materials using a series of derivatizing molecules. Due to the promise of this technology, a major pharmaceutical company has agreed to collaborate with Bend Research by screening the derivative libraries for bioactivity for a broad range of therapeutic uses.